Epigenetic crosstalk between hypoxia and tumor driven by HIF regulation
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(2020) 39:224
REVIEW
Open Access
Epigenetic crosstalk between hypoxia and tumor driven by HIF regulation Tiansheng Li1,2, Chao Mao1,2, Xiang Wang3, Ying Shi1,2* and Yongguang Tao1,2,3*
Abstract Hypoxia is the major influence factor in physiological and pathological courses which are mainly mediated by hypoxia-inducible factors (HIFs) in response to low oxygen tensions within solid tumors. Under normoxia, HIF signaling pathway is inhibited due to HIF-α subunits degradation. However, in hypoxic conditions, HIF-α is activated and stabilized, and HIF target genes are successively activated, resulting in a series of tumour-specific activities. The activation of HIFs, including HIF-1α, HIF-2α and HIF-3α, subsequently induce downstream target genes which leads to series of responses, the resulting abnormal processes or metabolites in turn affect HIFs stability. Given its functions in tumors progression, HIFs have been regarded as therapeutic targets for improved treatment efficacy. Epigenetics refers to alterations in gene expression that are stable between cell divisions, and sometimes between generations, but do not involve changes in the underlying DNA sequence of the organism. And with the development of research, epigenetic regulation has been found to play an important role in the development of tumors, which providing accumulating basic or clinical evidences for tumor treatments. Here, given how little has been reported about the overall association between hypoxic tumors and epigenetics, we made a more systematic review from epigenetic perspective in hope of helping others better understand hypoxia or HIF pathway, and providing more established and potential therapeutic strategies in tumors to facilitate epigenetic studies of tumors. Keywords: Hypoxia, Hypoxia-inducible factors (HIFs), Tumors, Epigenetic regulation, Crosstalk, Therapeutic strategy
Background Low oxygen tension (hypoxia) arises from excessive oxygen consumption to supports the demand of rapid proliferation, and abnormalities in the structure and function of blood vessels within solid tumors [1–4]. Mounting clinical and experimental evidences have revealed that hypoxia-related oxygen pressure contributes to higher metastasis and mortality rates [5–7]. Hypoxia occurs in 90% of solid tumors, which has been regarded as a hallmark of cancer [8–10]. In addition, hypoxia often plays a key role in tumor progression and tolerance to targeted therapies [11, 12]. Massive efforts have * Correspondence: [email protected]; [email protected] 1 NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China Full list of author information is available at the end of the article
been brought about in investigating hypoxia due to its significantly clinical implication. Tumor-associated metabolic alterations at multi-steps of metastasis have been observed in clinical samples via ever-acceler
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